Chronic fatigue syndrome researcher Mikovits, who championed link to XMRV, to publish book

In an announcement on Age of Autism, co-author Kent Heckenlively gives a taste of what readers might find in the book, titled PLAGUE – One Scientist’s Intrepid Search for the Truth about Retroviruses, Chronic Fatigue Syndrome, Autism, and Other Diseases:

In many ways I felt her story, especially the campaign of persecution against her, mirrored that of many other honest scientists who have looked for answers to the questions raised by these diseases.

Sadly, the narrative around CFS and autism has left many of those affected feeling abandoned and ignored: CFS sufferers because they were initially told they didn’t have a “real” condition, parents of children with autism because they were unable to receive the treatment their children needed or the support they yearned for. In both cases, some vocal members of those patient communities have latched onto theories — CFS and XMRV, autism and vaccines — that hold no scientific water. They take the scientific rejection of those theories as either another abandonment or as proof of some larger conspiracy, even as researchers try to figure out what’s actually going on.

On July 22, 2009, a special meeting was held with twenty-four leading scientists at the National Institutes of Health to discuss early findings that a newly discovered retrovirus was linked to chronic fatigue syndrome (CFS), prostate cancer, lymphoma, and eventually neurodevelopmental disorders in children.

When Dr. Judy Mikovits finished her presentation the room was silent for a moment, then one of the scientists said, “Oh my God!” The resulting investigation would be like no other in science.

For Dr. Mikovits, a twenty-year veteran of the National Cancer Institute, this was the midpoint of a five-year journey that would start with the founding of the Whittemore-Peterson Institute for Neuro-Immune Disease at the University of Nevada, Reno, and end with her as a witness for the federal government against her former employer, Harvey Whittemore, for illegal campaign contributions to U.S. Senate Majority Leader Harry Reid.

On this journey Dr. Mikovits would face the scientific prejudices against CFS, wander into the minefield that is autism, and through it all struggle to maintain her faith in God, the American justice system and the profession to which she had dedicated her life. This is a story for anybody interested in the promise and peril of science at the very highest levels in our country.

Science is fully retracting the report “detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome” (1). Multiple laboratories, including those of the original authors (2), have failed to reliably detect xenotropic murine leukemia virus–related virus (XMRV) or other murine leukemia virus (MLV )–related viruses in chronic fatigue syndrome (CFS) patients. In addition, there is evidence of poor quality control in a number of specific experiments in the Report. Figure 1, table S1, and fig. S2 have been retracted by the authors (3). In response to concerns expressed about Fig. 2C [summarized in (4)], the authors acknowledged to Science that they omitted important information from the legend of this figure panel. Specifically, they failed to indicate that the CFS patient–derived peripheral blood mononuclear cells (PBMCs) shown in Fig. 2C had been treated with azacytidine as well as phytohemagglutinin and interleukin-2. This was in contrast to the CFS samples shown in Figs. 2A and 2B, which had not been treated with azacytidine.

Given all of these issues, Science has lost confidence in the Report and the validity of its conclusions. We note that the majority of the authors have agreed in principle to retract the Report but they have been unable to agree on the wording of their statement. It is Science‘s opinion that a retraction signed by all the authors is unlikely to be forthcoming. We are therefore editorially retracting the Report. We regret the time and resources that the scientific community has devoted to unsuccessful attempts to replicate these results.

MAR Consulting Inc., led by Drs. Frank Ruscetti and Judy Mikovits, seeks to understand complex and innovative biological issues to yield unbiased integrated, cutting-edge information for patients and physicians impacted by some of the most challenging chronic diseases. Utilizing their combined 75 years experience in tumor biology, immunobiology of retroviral-associated inflammatory diseases, cancer, stem cell biology, hematopoiesis, and drug development, MAR focuses on research projects, consulting (to patients doctors, academia, and industry) and lecturing without the restrictive authority of vested interest groups, following Thomas Jefferson’s dictum: “Here we are not afraid to follow the truth wherever it may lead, nor to tolerate error so long as freedom is left free to combat it.”

Another twist to this story is that the CFS community still appears wedded to the infectious agent theory. In 2011 a research trust/foundation was established – http://www.cfinitiative.org – with $10m of private money to spend over 3-4 years on CFS research. Much of their research appears directed at pathogen discovery in CFS patient tissue banks. They don’t appear to have updated their website in quite some time, because they tout a collaboration with Lipkin at Columbia to study the XMRV/CFS link, but don’t mention Lipkin’s 2012 publication which totally debunks that link. It’s also notable that Lipkin’s paper doesn’t acknowledge support from CFI. $10m is a decent amount of money, so one would hope some new directions for CFS research can come out of this, but the CFI website doesn’t point toward anything beyond the old XMRV paradigm.

“The CFS community” is very diverse, and different people prefer different theories about the etiologies of the disease. The idea that it is caused by an infectious agent is one possibility that deserves serious study, even though XMRV is almost certainly not the responsible agent. Other theories also deserve serious study. It’s a good thing that private money is coming in to study these things, because the federal government is providing only 5 million dollars a year for an illness that affects a million Americans and costs the US economy $24 billion a year.

There’s a huge difference between infectious agent theories in general and XMRV in particular in ME/CFS. Infectious agent theories in the field of ME/CFS research are still very much under discussion due to a) the numerous findings of aberrant immune activation in ME/CFS patients, b) the fact that many ME/CFS patients fall ill following a sudden, ‘flu-like’ illness from which they never recover, and c) the fact that prolonged post-infectious, aka ‘chronic’, fatigue syndromes following any number of relatively common infections (EBV/infectious mononucleosis, Coxellia Burnetti/Q-fever, Ross-River virus, SARS, West Nile virus, acute Lyme disease, Giardia lamblia, etc) are an emerging area of research. However to compare ‘infectious agent theories’ in general with XMRV in particular is ignorant and incorrect. Infectious agents continue to be a legit area of research; XMRV is in the trash and has been for quite some time. You can technically describe the fringe theories re: XMRV espoused by the couple dozen (at most?) posters on various forums as ‘some vocal members of the ME/CFS community’, but you could also technically describe fringe theories about any number of issues such as 9/11 truthers, UFO’s, etc. as coming from ‘some vocal members of the blogging community’. It’s not exactly a fair comparison.

As for the CFI, the reason why ‘Lipkin’s paper doesn’t acknowledge support from CFI’ is because the paper(s) which were funded by the CFI haven’t been published yet, although one is supposedly on the way that will produce some apparently novel findings (1,2,3). The Lipkin/XMRV study money came from the NIH.

“some vocal members of those patient communities have latched onto theories — CFS and XMRV, autism and vaccines — that hold no scientific water.”

Am I missing something, or is that comparison rather off? Since the Lipkin paper, I don’t think I’ve seen vocal members of the CFS community arguing that XMRV causes CFS. It is the internet, so there must be some people claiming this is the case, but nothing like the sort of community that surrounds autism and vaccines.

Also, in explaining why there was such distrust and animosity around autism I think it’s worth mentioning the ‘refrigerator parents’, psychoanalysis, etc quackery that had been promoted for so long – it wasn’t just the lack of effective treatments that was the problem.

The comment you quoted uses classic “weasel words”, which makes the point rather ambiguous. Yes there are (literally a handful) of such vocal individuals, including one lady that annoyingly spams lots of blogs to gain support for her fringe theory.

But I’d say over 99% of the vocal CFS community, have moved on. Those who have a keen interest in the research have a great deal of respect for Ian Lipkin and his team, including ongoing research led by Mady Hornig.

@Vhedwid writes, “Another twist to this story is that the CFS community still appears wedded to the infectious agent theory… much of their research appears directed at pathogen discovery in CFS patient tissue banks”, as if suspicion and research pursuit of infectious involvement in Myalgic Encephalomyelitis is some cardinal sin. To anyone who has ever had the ‘flu – and then developed M.E. (or ME/CFS, as the press often describes it) – the infectious viral connection is screamingly obvious. To any patient who has developed M.E. following an infectious cluster, the infectious connection demands exploration (think Lyndonville, Royal Free Hospital, and Incline Village). To any physician who really listens to their patients – and then researches the same cytokines found in M.E. and the ‘flu, the infectous overtones are also screamingly obvious.

Decades ago, AIDS patients were discredited for dying of “too many” viruses. There was no such thing as AIDS, the mantra went, because some died of what would be later recognized as Kaposi’s Sarcoma; others died of pneumonia. The grim reality that retroviruses create immunodeficiency which predisposes the host to sickness and death from a multitude of potential viruses, of course, was the underlying reality.
The same bigotry is reflected in crushingly ignorant comments. One doesn’t need to look far to learn that indeed the viral connection with M.E. is real and robust. The nuance is that while viruses may precipitate M.E., and opportunistic viruses may take hold, their detection is no small matter. The more refined researchers are recognizing that a host of immune insults may “precipitate” M.E.: exposure to toxins; sudden physical insults such as vehicle accidents; severe stress. This points the contemplative scientist in the direction of epigenetic assault. And AIDS specialists, or virologists such as Dr Dharam Ablashi (co-discoverer of HHV-6) know full well that negative blood analysis can yet be trumped by the finding of viral reservoirs in the tissues.

And so the search for viral footprints in M.E. continues – even as thoughtful scientific luminaries acknowledge that the constellation of viruses associated with M.E. may well point to a retrovirus; possibly even a recombinant Human Endogenous Retrovirus, re-activated but not necessarily replication-competent, which might induce a state of immunodeficiency that creates a perfect storm of immune activation or suppression, and viral vulnerability. And there are even more nuances to the possibility of retroviral involvement; indeed, mere proteins produced by protein fragments of viruses are widely known to be capable of producing disease. In other words, such intellectual curiosity from the likes of Dr Mikovits is welcomed.

Anyone serious about understanding ME/CFS (and its many subgroups) does not need to look far to see a plethora of justifiable interest in infectious connection and immune dysfunction. As it happens, just this month there is a Symposium: http://chronicfatigue.stanford.edu/documents/2014StanfordME_CFSSymposiumBrochurefinal.pdf ; and an international conference: http://www.iacfsme.org/Conferences/2014Conference/tabid/532/Default.aspx ) hosted by no less than Stanford University Department of Medicine, on this black sheep of medicine: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. And wonder of wonders, Stanford University even has a Chronic Fatigue Initiative too (http://chronicfatigue.stanford.edu/ ). Not surprisingly – at least to anyone remotely informed on the science of M.E. – there is vibrant interest in immune dysfunction and viral infection associated with this disease. For example, Natural Killer Cell dysfunction – recognized by any marginally informed student of M.E. as a hallmark of the disease, and a predisposer of viral infection – is prominently featured at this conference.

It is no coincidence that Stanford Infectious Disease specialist Dr Jose Montoya – a fixture of the ME/CFS research world for decades – is renowned for returning patients to work and life, following treatment by antivirals. It is testimony to his open and enquiring mind that Dr Montoya is known to be speculating whether the clinical effect of antivirals in M.E. may be in part due to their anti-inflammatory effect. In other words, the worlds of Infectious Disease and Immunology appear to be colliding in M.E., as thoughtful scientists such as Dr Ian Lipkin ponder the possibility of a viral “Hit and Run” that leaves the immune system in tatters. So it is no accident that Dr Montoya says this about M.E.: “Chronic Fatigue Syndrome is arguably the greatest medical and scientific challenge of our time.”

The breathless finger-pointing-at-infectious-paranoia, embodied by colossally poorly-informed wannabe’s, (or “if-I-don’t-understand-it-it’s-all-in-your-head” potential psychologizers) makes great print, but frankly is an embarrassment to the genuine pursuit of answers to such complex and devastating diseases such as M.E.

Quasi-truth-finders need to cast a wider net to begin to see the burgeoning excitement in the global scientific community as a result of what Retraction Watch would have one believe was a unilateral debacle: the XMRV saga. Far from feeling “abandoned and ignored” as Retraction Watch writes, anyone who has pined for more robust science on M.E. is thrilled at the pedigree of scientists who have joined the hunt for the cause – and treatments and cure – for M.E., AS A RESULT of the international profile and momentum provided by the hunt for XMRV by Dr Mikovits and ilk. After all, the research world jumped on the plausability of XMRV because to the informed minds, it made so much damn sense.

For example, Dr Uber-scientist Eric Schadt, a world-renowned computational biologist who has joined the hunt, is ideally positioned to study the genetic complexities of such a complex disease as M.E.. To quote from his profile: “He is known for calling for a shift in molecular biology toward a network-oriented view of living systems to complement the reductionist, single-gene approaches that currently dominate biology in order to more accurately model the complexity of biological systems.”. In other words, where M.E. is concerned, simpletons beware.

Ultimately patients don’t care what the etiology is, as long as it leads to treatments and a cure for this horrendous suffering from an invisible disease whose seriousness is derided by small minds. So Hats Off! And Bravo to Drs Mikovits and Ruscetti for their dictum: “Here we are not afraid to follow the truth wherever it may lead, nor to tolerate error so long as freedom is left free to combat it.”

“it’s not hard to see the parallels Heckenlively is drawing between Mikovits and Andrew Wakefield”

In addition, Mikovits has appeared at Ed Arranga’s “Autism One” conference, which is somewhat notorious for ejecting “spies” and having presentations on using bleach enemas to “treat” children with autism (Kerri Rivera) in the past. This also involved a booth hawking the VIP Dx XMRV “test.” (Arranga was further behind the “Wakefield Justice Fund.”)

I have M.E. I also have a natural killer cell function of less than 3%, the 37 kDa Rnase-L defect (discovered simultaneously by Robert Suhadolnik of Temple in Philadelphia and Bernard Le Bleu of France in the mid-1990s). I was in some of the earliest research into HHV-6 Variant A by Dr. Dharam Ablashi, who co-discovered the virus and it’s two variants while at NCI (and having HHV-6A does not make you automatically an HIV-denier – it just makes you someone infected with HHV-6A), and recurring EBV. I was found to have HHV-6 and CMV active in my spinal fluid.

At the same time, I had intense pain in the back of my neck and eyes, glands that felt like golfballs, recurring severe headaches, and muscle pain. I had ataxia, absence seizures, blackouts, dyslexia, expressive dysphasia, disorientation, light sensitivity, and massive confusion (to the point where I once poured an entire pot of coffee into a silverware drawer). As the disease progressed, I became primarily bedridden, unable even to brush my own teeth.

I had abnormal SPECT scans and CPET scores so low I would be considered a cardiac risk doing the lightest exercise.

I am fortunate; I do well on the experimental immune modulator Ampligen. I have to commute 100 miles by train twice a week to get it, and since it is still Phase III, I have to pay cash, but it’s worth it to be able to read, walk, drive a car, and be coherent again (although there are still things seriously wrong).

Ignore spammers and look at the serious research (as cited in the excellent comments by ” Science_Based” above. It is amazing that any serious scientific research can be done when NIH allocates roughly $2 per patient to this disease (less than they allocate to male-pattern baldness; MS, a similar disease and one tat is hardly over-funded, gets 100 times that amount). By pooling the little money the patient community has, we are getting some good private research from Stanford, Columbia, Cornell, Mt. Sinai-NY, Univ of Miami, and other reputable research universities. But we desperately need funding from NIH for larger studies to replicate all the current findings.

I really don’t care whether or not I have a retrovirus (although I am curious about how you get antibodies to a lab contaminant …). My disease is already well-defined by replicable testing. We just need to get the psychiatrists, insurance companies, and amateurs out of the process – not to mention those who think only retroviruses can be serious – and stick to the science.

(I would add to the references above the HHV-6 Foundation , which holds high-quality international research conferences every other year on the beta herpesviruses, as a source of cutting-edge information for scientists.)